Technology Overview

Heme Oxygenase Overview: The HO pathway is the major mechanism the human body uses to prevent the harmful effects of free heme, which is a naturally occurring substance in the human body. When red blood cells lyse (break open), they release hemoglobin into the blood or tissues. Hemoglobin is made up of heme bound to the protein “globin”, and hemoglobin quickly releases heme from the globin. Free heme is a potent inflammatory stimulus that leads to cell injury and death.

Critical Protective Pathway: HO is recognized as a critical protective pathway for its anti-inflammatory and anti-apoptotic actions. Substantial data demonstrates the protective effects of Heme Oxgenase-1 (HO-1), the isoform of the enzyme that is distributed throughout the body. This pathway has been shown to be activated by low doses of CO, acting as a gasotransmitter. Moreover, CO itself has been demonstrated to possess potent anti-inflammatory and anti-apoptotic properties that amplify the protective actions of HO. This pathway has also been shown to modulate a wide spectrum of additional genes linked to inflammation and apoptosis, including Nrf2, Nf-ĸB, the STAT3 pathway, the CREBH pathway, the c-Jun-NH2-terminal kinase pathway, and p38 MAPK.

Safety and Tolerability of CO: Studies show CO administered as an exogenous gasotransmitter mimics the protective effects of HO-1, reducing inflammation and cell death. The safety and tolerability of low levels of CO have been demonstrated by others in four completed Phase 1 and three completed Phase 2 clinical studies using various forms of CO administration other than the Hillhurst product. Ten additional clinical trials by others are ongoing.

Hillhurst’s proprietary products rely on oral (HBI-002) or intravenous (HBI-137) administration of CO gasotransmitter that has been shown to up-regulate the heme oxygenase enzyme and otherwise provide anti-inflammatory and anti-apoptotic effects.